ω-Aryl-inter-oxa-12,13(E)-didehydro-13,14-dihydro-PGD1 compounds

ABSTRACT

Prostaglandin analogs with the following cyclopename ring structure: ##STR1## are disclosed along with intermediates useful in their preparation and processes for their preparation. These analogs are useful for some of the same pharmacological purposes as the prostaglandins, particularly and especially as blood platelet aggregation inhibitors.

The present application is a divisional application of Ser. No. 809,249, filed June 23, 1977; which is a divisional application of Ser. No. 614,244, filed Sept. 17, 1975, now pending. Likewise, U.S. Ser. No. 809,248, filed June 23, 1977 is a divisional application of Ser. No. 614,244.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from Ser. No. 809,248, now pending issuance as a United States patent. 

I claim:
 1. A prostaglandin analog of the formula ##STR2## WHEREIN D is ##STR3## wherein Y is ═CH--CH₂ --; wherein Z₅ is(1) --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂ --, (2) --(ch₂)₂ --o--(ch₂)_(g) --CH₂ --, or (3) --(CH₂)₃ --O--(CH₂)_(g) --, wherein g is one, 2, or 3; Wherein M₁ is ##STR4## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; Wherein L₁ is ##STR5## or a mixture of ##STR6## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is hydrogen or fluoro only when the other is hydrogen or fluoro; Wherein Z₃ is oxa or methylene; Wherein T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl, with the further proviso that Z₃ is oxa only when R₃ and R₄ are hydrogen or methyl, being the same or different; and R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 2. A compound according to claim 1, wherein M₁ is ##STR7##
 3. A compound according to claim 1, wherein M₁ is ##STR8##
 4. A compound according to claim 1, wherein D is ##STR9##
 5. A compound according to claim 1, wherein Z₃ is methylene.
 6. A compound according to claim 5, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 7. A compound according to claim 6, wherein g is one.
 8. A compound according to claim 7, wherein R₅ and R₆ are both hydrogen.
 9. A compound according to claim 8, wherein R₃ and R₄ are both hydrogen.
 10. 5-Oxa-17-phenyl-18,19,20-trinor-13,14-dihydro-12,13(E)-didehydro-9-deoxy-PGD.sub.1, a compound according to claim
 9. 11. A compound according to claim 4, wherein Z₃ is oxa.
 12. A compound according to claim 11, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 13. A compound according to claim 12, wherein g is one.
 14. A compound according to claim 13, wherein R₅ and R₆ are both hydrogen.
 15. A compound according to claim 14, wherein R₃ and R₄ are both hydrogen.
 16. 5-Oxa-16-phenoxy-17,18,19,20-tetranor-13,14-dihydro12,13(E)-didehydro-9-deoxy-PGD₁, a compound according to claim
 15. 17. A compound according to claim 4, wherein D is ##STR10##
 18. A compound according to claim 17, wherein Z₃ is methylene.
 19. A compound according to claim 18, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 20. A compound according to claim 19, wherein g is one.
 21. A compound according to claim 20, wherein R₅ and R₆ are both hydrogen.
 22. A compound according to claim 21, wherein R₃ and R₄ are both hydrogen.
 23. 5-Oxa-17-phenyl-18,19,20-trinor-12,13(E)-didehydro-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₁, a compound according to claim
 22. 24. A compound according to claim 17, wherein Z₃ is oxa.
 25. A compound according to claim 24, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 26. A compound according to claim 25, wherein g is one.
 27. A compound according to claim 26, wherein R₅ and R₆ are both hydrogen.
 28. A compound according to claim 27, wherein R₃ and R₄ are both hydrogen.
 29. 5-Oxa-16-phenoxy-17,18,19,20-tetranor-12,13(E)-didehydro-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₁, a compound according to claim
 28. 30. A compound according to claim 3, wherein D is ##STR11##
 31. A compound according to claim 30, wherein Z₃ is methylene.
 32. A compound according to claim 31, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 33. A compound according to claim 32, wherein g is one.
 34. A compound according to claim 33, wherein R₅ and R₆ are both hydrogen.
 35. A compound according to claim 34, wherein R₃ and R₄ are both hydrogen.
 36. 5-Oxa-17-phenyl-18,19,20-trinor-12,13(E)-didehydro-13,14-dihydro-9β-PGD.sub.1, a compound according to claim
 35. 37. A compound according to claim 30, where Z₃ is oxa.
 38. A compound according to claim 37, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 39. A compound according to claim 38, wherein g is one.
 40. A compound according to claim 39, wherein R₅ and R₆ are both hydrogen.
 41. A compound according to claim 40, wherein R₃ and R₄ are both hydrogen.
 42. 5-Oxa-16-phenoxy-17,18,19,20-tetranor-12,13(E)-didehydro-13,14-dihydro-9β-PGD₁, a compound according to claim
 41. 43. A compound according to claim 3, wherein D is ##STR12##
 44. A compound according to claim 43, wherein Z₃ is methylene.
 45. A compound according to claim 44, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 46. A compound according to claim 45, wherein g is one.
 47. A compound according to claim 46, wherein R₅ and R₆ are both hydrogen.
 48. A compound according to claim 47, wherein R₃ and R₄ are both hydrogen.
 49. 5-Oxa-17-phenyl-18,19,20-trinor-12,13(E)-didehydro-13,14-dihydro-PGD₁, a compound according to claim
 48. 50. A compound according to claim 43, wherein Z₃ is oxa.
 51. A compound according to claim 50, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 52. A compound according to claim 51, wherein g is one.
 53. A compound according to claim 52, wherein R₅ and R₆ are both hydrogen.
 54. A compound according to claim 53, wherein R₃ and R₄ are both hydrogen.
 55. 5-Oxa-16-phenoxy-17,18,19,20-tetranor-12,13(E)-didehydro-13,14-dihydro-PGD₁, a compound according to claim
 54. 